A comparitive study between tranexamic acid and epsilon-amino-caproic acid in reducing post-operative bleeding in patients undergoing on pump cabg surgeries.

Research Article | DOI: https://doi.org/10.31579/2693-2156/004

A comparitive study between tranexamic acid and epsilon-amino-caproic acid in reducing post-operative bleeding in patients undergoing on pump cabg surgeries.

  • Rajeev Nair 1
  • Satish Kumar Mishra 2*
  • Parli Raghavan Ravi 3
  • Avanish Bhardwaj 4

1 Anesthesiology HOD, Department of Anesthesiology and critical care Command Hospital Airforce Bangalore, India.
2 DM Cardiac Anesthesia, Department of Anesthesiology and critical care Command hospital Airforce, Bangalore, India.
3 DNB Anesthesia, Department of Anesthesiology and critical care Command hospital Airforce Bangalore, India.
4 DM Neuro Anesthesia, Department of Anesthesiology and critical care Command hospital Airforce, Bangalore, India.

*Corresponding Author: Satish Kumar Mishra, Anesthesiology HOD Departement of Anesthesiology and critical care Command Hospital Airforce, Bangalore, India.

Citation: Rajeev Nair, Satish Kumar Mishra, Parli Raghavan Ravi, Avanish Bhardwaj, (2020) A comparitive study between tranexamic acid and epsilon-amino-caproic acid in reducing post-operative bleeding in patients undergoing on pump cabg surgeries. J Thoracic Disease and Cardiothoracic Surgery, 1(1); DOI: 10.31579/2693-2156/004

Copyright: © 2020 Satish Kumar Mishra, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 27 May 2020 | Accepted: 09 June 2020 | Published: 12 June 2020

Keywords: TA: tranexamic acid; EACA: epsilon-amino-caproic acid; CPB: cardio pulmonary bypass; PRBC: packed red blood cell, FFP: fresh frozen plasma

Abstract

The amount of strain that cardiac surgery exerts on blood bank services is an example that emphasises the need for multimodel blood conservation stratergy. The most common factor which is being attibutable to increased bleeding after cardiac surgery is hyperfibrinolysis. Thererfore the use of antifibrinolytics during high risk cardiac surgery becomes inevitable. Commonly used  antifibrinolytic  include Tranexamic Acid(TA) and Epsilon-amino-caproic acid (EACA) .The aim of our study was to compare the effectiveness of both TA and EACA in reducing post surgical bleeding in on-pump CABG surgeries and to asses the post operative complications associated with its use.Material and Methods After obtaining informed written consent,approval of ethics and research commitee patients who were scheduled for on-pump CABG were included in the study.Patients were divided into two groups randomly by using a comupter generated randomized block design namely group TA(n=40) and group EACA (n=40). TA group received tranaxamic acid at a dose of 10mg/kg IV over 20 min at the time of induction then 1-2 mg/kg in CPB prime followed by  1 mg /kg/hr infusion during surgery. Group EACA received EACA in a dose of 100mg/kg/IV over 20 min at he time of induction then 5-10mg/kg in CPB prime followed by 10mg/kg/hr infusion during surgery . Pateints were assessed for blood loss and were monitored for fibrinogen level and D- dimer levels, Re-exploration and  post operative complications. Result Primary outcomes like bleeding at 4hrs, there was no significant difference between the groups but when total bleeding at 24 hrs was compared there was a significantly lesser bleed in group TA group compared to group EACA (P=0.0022).The requirement of PRBC in group TA was for 3 patients,where as in EACA group 4 patients required PRBC (P>0.05).There was no significant difference in the rate of post operative complications between the groups.(P>0.05) .Conclusion from our study we concluded  that both TA & EACA effectively inhibits fibrinolysis during on pump CABG surgery and thus results in decreased post operative bleeding.When compared between the two, TA was slightly better with respect to post operative bleeding at 24hrs.Our study also re emphesized the fact that neither of the drug led to any additional risk of post operative thrombotic complications.

Introduction

For decades the most common indication for blood transfusion is perioperative bleeding and cardiac surgery ranks high on the list. The reason which is being attributable to this complication is the institution of Cardio Pulmonary Bypass (CPB). CPB leads to series of events like compliment activation, platelet Activation and increased fibrinolysis which contributes to increased post operative bleeding1 .Post operative bleeding in itself carries a high risk for in hospital mortality. Cardiac surgical patients who are taken up for re exploration due to bleeding carry a four fold increase in mortality and sternal wound infection 2. Therefore a multimodal approach is recommended to reduce perioperative bleeding which includes the use of antifibrinolytic agents.

Anti fibrinolytic agents have been used during cardiac surgery to reduce the risk of post operative bleeding. Most commonly used antifibrinolytic agents include Aprotinin and lysine analogs (Tranexamic acid TA and E- amino caproic acid EACA).

Aprotinin is a serine protease inhibitor which inhibits multiple proteases like plasmin, kallikrein, trypsin, and activated factor XII, there by reducing blood loss.in 2007 a prospective study on high risk patients undergoing cardiac surgery know as Blood conservation using Antifibrinolytics in a Randomized Trial (BART) reported an increased mortality with use of aprotonin compared to lysine analogs 3 . Later due to warning from Food and Drug administration (FDA) ,Bayer health care withdrew aprotinin from the market. Now the Society of Thoracic Surgeons (STS) guidelines 4  recommend the use of anti‐fibrinolytic agents (only lysine analogues), as a strategy to reduce perioperative blood loss during cardiac surgery.   

Tranexemic acid (TA) is a synthetic antifibrinolytic that blocks lysine binding site on plasminogen molecule, thus inhibiting the interaction with plasmin and fibrin which leads to decreased post operative bleeding5-6. Similarly EACA is a synthetic lysin analog which reduces the rate of plasmin formation and further decreases the degradation of fibrin to fibrin degradation product (FDP)7. Apart from this EACA also has a platelet sparing action which leads in inhibition of plasmin mediated platelet injury8 .

Both TA and EACA have been shown to decrease post operative bleeding associated with CPB. However there are no large studies comparing the effectiveness of both drugs in pateints undergoing on pump CABG surgeries.

The aim of our study was to compare the effectiveness of both TA and EACA in reducing post surgical bleeding in on-pump CABG surgeries with regards to the amount of blood loss at 4Hrs and 24Hrs as the primary outcome. The secondary outcome of our study included the rate of transfusion of packed red blood cell (PRBC), fresh frozen plasma(FFP) and platelets, re exploration rates, post operative  D-dimer and fibrinogen levels.

Material and Methods

After obtaining informed written consent, approval of ethics and research committee patients who were scheduled for on-pump CABG were included in the study. This study was carried out between June 2019 to Feb 2020. Patients with concomitant valvular heart disease, recent Myocardiac Infarction (MI<4wks) Ejection Fraction <40%, Preexisting neurological, pulmonary or hepatic dysfunction were excluded from the study.

Patients were divided into two groups randomly by using a computer generated randomized block design namely group TA(n=40) and group EACA (n=40). In both the group under strict aseptic precaution under local anesthesia a wide bore peripheral IV cannula, right radial artery cannulation and right femoral artery cannulation was done for continuous hemodynamic monitoring. Anesthesia was induced with Inj etomidate (0.2mg/kg), Inj Fentanyl (3-5 ug/kg) and Inj Rocuronium (0.8-1mg /Kg). After induction of patient right internal jugular vein cannulation was done with 7.5 Fr Triple lumen catheter and PA catheter was inserted. Anesthesia was maintained with air and oxygen (50%),sevoflurane (1-3%) and Inj Atracurium (0.5-1mg/Kg). After sternotomy and heparinization CPB was established once ACT was >420 Sec.

TA group received tranaxamic acid at a dose of 10mg/kg IV over 20 min at the time of induction then 1-2 mg/kg in CPB prime followed by  1 mg /kg/hr infusion during surgery. Group EACA received EACA in a dose of 100mg/kg/IV over 20 min at he time of induction then 5-10mg/kg in CPB prime followed by 10mg/kg/hr infusion during surgery . Later Inj Protamine was administered to reverse the effect of Heparin.

After the completion of surgery patients were shifted to ICU and were assessed for blood loss at 4 hrs and 24 hrs after shifting. Indication for transfusion of PRBC was a haemoglobin level of < 8gm/dl. FFP was transfused if post operative drain was > 250ml/hr in first hour. Platelet transfusion was indicated if platelets counts were <50000/mm3. The degree of fibrinolysis was measured by  Thromboelastography (TEG),(Hemostasis system, Haemoscope corporation USA)

            Other parameters which were monitored included fibrinogen level and D- dimer levels at 4 hrs and 24 hrs. Re-exploration of case was considered if the bleeding was > 300ml/hr in first 2 hrs or if >200 ml/hr for 4 consecutive hrs, with normal coagulation data. Patients were also observed for post operative complications like MI, Stroke, Deep vein thrombosis (DVT),renal dysfunction and seizures for 72 hrs.

Figure 1: Randomization, group allocation and assessment of patients
 

 

Results

Demographic variables like age,weight,height, male-female ratio were comparable in both groups. (Table-1) 

TA= Tranexamic Acid    EACA= Epsilon-amino-caproic-acid                                                                                                     
 Table 1. Baseline Demography

The cross clamp time & duration on CPB were also comparable in both groups (Table-2). 

Table 2. Intra operative time and intervention

Primary outcomes like bleeding at 4hrs, there was no significant difference between the groups but when total bleeding at 24 hrs was compared there was a significantly lesser bleed in group TA group compared to group EACA (P=0.0022).

The requirement of PRBC in group TA was for 3 patients,where as in EACA group 4 patients required PRBC (P>0.05). One pateint in each group required FFP transfusion (P>0.05).Both the groups did not require any platelet transfusion & the transfusion rate was non-significant between the groups. Both the groups had no re exploration due to excessive bleeding (Table-3).

PRBC: Packed Red Blood Cell, FFP: Fresh Frozen Plasma                                                                                                          Table 3. Primary and secondary Outcome

There was no significant difference in the rate of post operative complications between the groups. (P>0.05) (Table-4),

MI: Myocardial Infarction DVT: Deep Vein Thrombosis PE: Pulmonary Embolism S. Cr: Serum Creatinine.
Table 4. Post Operative Complications

Statistical analysis was done with SPSS software version 19.0 normality of the test were checked using Kolmogorov-smirnov test. The values which were obtained were analyzed and were expressed as mean +/- Standard Deviation (SD) and median +/- range. For continuous variables for parametric data,Indepedent's test were used and for non parametric data Mann-Whitney u test were used. For categorical data, Chi-Square test or fisher's exact test were used. A P Value of <0.05 was considered to be statistically significant.

Discussion

On pump CABG is associated with increasesd risk of post operative bleeding compared to OPCAB9-10 reason best attributable to use of CPB, which is associated with increased fibrinolysis & increased concentration of inflammatory mediators,which has urged researchers all around the world to investigate the probable role of antifibrinolytics in on pump cardiac surgeries 11.

            In our study we found that there was no significant difference in the amount of post operative bleeding at 4 hours between the groups however at 24 hrs there was a significant difference between both the groups with lesser bleeding in group TA compared  to group EACA. This may be due to the fact the TA is 10 times more potent than EACA12. Similar findings were obtained in a study comparing TA & EACA with placebo conducted by Karski Et al13.

       Chauhan Et al 14 & Faure Et al 15while comparing both the drugs showed that there was no significant difference in the rate of post operative transfusion of PRBC,FFP / Platelet or the rate of re-exploration for excessive bleeding,which was comparable with our study.

            Post operative blood transfusion after CABG is associated with increased long term mortality16. .Therefore the role of these drugs in reducing the transfusion rate after on pump CABG is very significant. There were no difference in the rate of post operative copmlications between the gropus. Hardy Et al in his study while comparing both the drugs did not find any significant difference between  the drugs with regards  to post operative thrombo embolic complications17.

There are controversis with regards to the dosing of the drug .A high dose(20mg/kg) TA is associated with increased risk of post operative seizures and therfore a low dose (10mg/kg)  regiem is recommended18.Armelin et al compared the low dose and high dose TA regiem and found no difference with respect to amount of post operative blood loss or transfusion requirement19.In our study we used low dose TA dosing and did not find any significant post operative complications.

Conclusion

Based on the results of our study it can be concluded that both TA & EACA effectively inhibits fibrinolysis during on pump CABG surgery and thus results in decreased post operative bleeding.When compared between the two, TA was slightly better with respect to post operative bleeding at 24hrs.

            Our study also re emphesized the fact that neither of the drug led to any additional risk of post operative thrombotic complications & thus can potentially become an standard of care for blood conservation in patients undergoing on pump CABG.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad